Trial of Ondansetron as a Parkinson's HAllucinations Treatment
Palabras clave
Abstracto
Descripción
This study investigates whether ondansetron, a drug used to treat post-operative sickness, has a meaningful treatment effect on Parkinson's hallucinations, and whether the drug is safe and cost effective for use in the NHS. We will compare ondansetron to placebo (a tablet that looks identical but contains no drug) over 12 weeks treatment, with follow up (once treatment ends) for a further 12 weeks. We will also investigate whether treatment effects against hallucinations are related to improved processing of visual information. Assessments of symptoms will be carried out during treatment (after 6 and 12 weeks), and once treatment ends (18, 24 weeks), to measure hallucinations, delusions (false beliefs), Parkinson's symptoms (tremor, anxiety, sleep disturbance), memory, quality of life, possible side-effects such as constipation and headache, and the proportion of people who drop out due to side effects, or require additional treatment for their hallucinations. Blood drug concentration (measured after 6 and 12 weeks) will provide information on how quickly the drug is cleared from the body, and how this relates to treatment effects and side-effects, to guide future prescribing in people with Parkinson's. Based on knowledge of the average hallucinations scores in previous Parkinson's treatment studies, 216 people will be needed for the study to detect a meaningful treatment effect. The study will run for 4 years and involves a series of linked stages: (1) Trial set up across 15-20 UK centres; (2) Recruitment over 2 years; (3) Completion of follow up; and analysis, publication and dissemination of results.
fechas
| Verificado por última vez: | 10/31/2019 |
| Primero enviado: | 11/14/2019 |
| Inscripción estimada enviada: | 11/14/2019 |
| Publicado por primera vez: | 11/18/2019 |
| Última actualización enviada: | 11/14/2019 |
| Última actualización publicada: | 11/18/2019 |
| Fecha de inicio real del estudio: | 03/31/2020 |
| Fecha estimada de finalización primaria: | 03/31/2022 |
| Fecha estimada de finalización del estudio: | 03/31/2023 |
Condición o enfermedad
Intervención / tratamiento
Drug: Ondansetron 8mg or matched placebo
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| Active Comparator: Active Treatment Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.
The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6). Dose escalation will be guided by telephone safety monitoring prior to each dose increase, and a face to face assessment at the end of week 6. | |
| Placebo Comparator: Matched placebo Participants randomised to the placebo treatment arm will take 8-24mg/day of matched placebo.
The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6). Dose escalation will be guided by telephone safety monitoring prior to each dose increase, and a face to face assessment at the end of week 6. |
Criterio de elegibilidad
| Edades elegibles para estudiar | 18 Years A 18 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | Inclusion Criteria: 1) Adults aged over 18 years. 2) Meet MDS criteria for Parkinson's disease. 3) Score of 3 or more on the SAPS-H visual hallucinations item, indicating the presence of visual hallucinations at least weekly in the previous month. 4) Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity. 5) Score of 4 or more on CGI-S, indicating moderate symptom severity. 6) On a stable dose of anti-Parkinson's medication, cholinesterase inhibitor or memantine for at least 28 days. 7) Capacity to give informed consent or, if lacking, legal representative able to give consent. 8) Pre-menopausal women, and men whose partners are of child bearing potential will agree to use effective contraception. 9) If treated with an antipsychotic drug at the time of enrolment, can still participate, provided the drug is stopped the day before trial medication is commenced. - Exclusion Criteria: 1) Bradycardia (<50 bpm) (rescreen if reversible). 2) Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening. 3) Severe hepatic failure (bilirubin >50 micromole/L) 4) Prescribed apomorphine (if apomorphine is discontinued, rescreen once stable on an alternative anti-Parkinson's treatment). 5) Prescribed tropisetron, granisetron, dolasetron. 6) History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 5). 7) Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days. - |
Salir
Medidas de resultado primarias
1. Visual hallucinations [SAPS (H) at 12 weeks]
Medidas de resultado secundarias
1. To establish whether ondansetron will reduce delusions [2, 4, 6, 12, 18, 24 weeks]
2. To determine safety and tolerability of ondansetron in people with Parkinson's [2, 4, 6, 12, 18, 24 weeks]
3. To establish whether ondansetron improves quality of life in people with Parkinson's [6, 12, 18, 24 weeks]
4. To investigate whether treatment effects will be associated with improved object recognition [6, 12 weeks]
5. To determine whether ondansetron is cost effective for NHS use [2, 4, 6, 12, 18, 24 weeks]
6. To investigate pharmacokinetic variability and how this relates to clinical outcome [6, 12 weeks]
